imipramine (Tofranil, Janimine)
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Introduction
Tradenames: Tofranil, Janimine.
Indications
- treatment of depression
- enuresis in children
- analgesic for neuropathic pain
- panic & anxiety disorders
- attention-deficit hyperactivity disorder (ADHD)[6]
Contraindications
- MAO inhibitor within 2 weeks
- fluoxetine within 2 weeks
- narrow angle glaucoma
- ineffective, & even harmful, for treating major depression in adolescents[7]
Dosage
Tabs: 10, 25, 50 mg.
Pharmacokinetics
- well absorbed following oral administration
- peak effect may take more than 2 weeks
- metabolized in the liver to desipramine (active)
- metabolized by cyt P450 1A2, 2C19, 2D6, 3A4
- elimination 1/2life 6-18 hours
- metabolites eliminated in the urine
- therapeutic range: 150-300 ng/mL.
elimination via liver
1/2life = 6-24 hours
protein binding = 76-96 %
elimination by hemodialysis = -
elimination by peritoneal dialysis = -
Adverse effects
- common (> 10%)
- dizziness, drowsiness, dry mouth, constipation, headache, increased appetite, nausea, weakness, unpleasant taste, weight gain
- less common (1-10%)
- blurred vision, confusion, delirium, hallucinations, difficult urination, eye pain, arrhythmias, fine muscle tremors, hypotension, nervousness, restlessness, parkinsonism, sexual dysfunction, diarrhea, excessive sweating, heartburn, insomnia
- uncommon (< 1%)
- agranulocytosis, leukopenia, eosinophilia, alopecia, anxiety, breast enlargement, galactorrhea, cholestatic jaundice, seizures, SIADH, tinnitus,testicular swelling, gingivitis, decreased lower esophageal sphincter tone, GERD, increased liver function tests, increased intraocular pressure, allergic reactions, photosensitivity, falls
- other
- moderate sedation
- moderate anti-cholinergic effects
- high incidence of orthostatic hypotension
- drug adverse effects of tricyclic antidepressants
- drug adverse effects of antidepressants
- drug adverse effects of psychotropic agents
Drug interactions
- coadministration enhances metabolism of imipramine
- coadministration decreases protein binding
- coadministration inhibits metabolism of imipramine
- reduced hypotensive effects of clonidine & guanethidine
- increased anticoagulant effect of warfarin
- increased CNS effects of CNS depressants & sympathomimetic agents
- additive effects in combination with anticholinergic agents
- agents which prolong the QT interval
- any drug which inhibits cyt P450 1A2, 2C19, 2D6, 3A4 can increase imipramine levels
- any drug which induces cyt P450 1A2, 2C19, 2D6, 3A4 can diminish imipramine levels
- drug interaction(s) of tricyclic antidepressants with physostigmine
- drug interaction(s) of benzodiazepines with antidepressants
- drug interaction(s) of antidepressants with benzodiazepines
- drug interaction(s) of NSAIDs with antidepressants
Laboratory
- imipramine in serum/plasma
- methods: HPLC, GLC, GC-MS, RIA, EIA
- interferences:
- iminodibenzyl & desipramine may contaminate dosage forms & contribute to metabolite concentrations
- mesoridazine interferes with HPLC assay
- specificity must be assessed with each test methods, because coelution with other TCA & metabolites may occur
- imipramine may be displaced from protein-binding sites by plasticizers in collecting devices
- other labs with Loincs
Mechanism of action
- inhibits serotonin & norepinephrine synaptic re-uptake
- tricyclic antidepressant
More general terms
Additional terms
- cytochrome p450 1A2 (cytochrome P3-450, phenacetin deethylase, cytochrome p450-4, CYP1A2)
- cytochrome P450 2C19 (cytochrome P450 2C17, cytochrome P450 11A, mephenytoin 4-hydroxylase, cytochrome P450 254C, CYP2C19)
- cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)
- cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)
- desipramine (Norpramin, Pertofrane)
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 56
- ↑ 6.0 6.1 Deprecated Reference
- ↑ 7.0 7.1 Le Noury J et al Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence. BMJ 2015;351:h4320 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26376805
Doshi P No correction, no retraction, no apology, no comment: paroxetine trial reanalysis raises questions about institutional responsibility. BMJ 2015;351:h4629 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26377109 <Internet> http://www.bmj.com/content/351/bmj.h4629
Henry D, Fitzpatrick T Liberating the data from clinical trials BMJ 2015;351:h4601 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26377210 <Internet> http://www.bmj.com/content/351/bmj.h4601